Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation

Title
Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation
Author(s)
장현욱유예[유예]양주혜[양주혜]이선[이선]황보경[황보경]황승락Yoshitaka Taketomi[Yoshitaka Taketomi]Makoto Murakami[Makoto Murakami]장영채[장영채]김철호[김철호]손종근
Keywords
FC-EPSILON-RI; NF-KAPPA-B; TYROSINE KINASE INHIBITOR; ARACHIDONIC-ACID; POLYGONUM-CUSPIDATUM; POLYMORPHONUCLEAR LEUKOCYTES; ALLERGIC INFLAMMATION; CYTOKINE PRODUCTION; CROSS-LINKING; CANCER CELLS
Issue Date
201112
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
BIOCHEMICAL PHARMACOLOGY, v.82, no.11, pp.1700 - 1708
Abstract
The high-affinity receptor for IgE (Fc epsilon RI)-mediated activation of mast cells plays an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. Emodin, a naturally occurring anthraquinone derivative in oriental herbal medicines, has several beneficial pharmacologic effects, such as anti-cancer and anti-diabetic activities. However, the anti-allergic effect of emodin has not yet been investigated. To assess the anti-allergic activity of emodin, in vivo passive anaphylaxis animal model and in vitro mouse bone marrow-derived mast cells were used to investigate the mechanism of its action on mast cells. Our results showed that emodin inhibited degranulation, generation of eicosanoids (prostaglandin D(2) and leukotriene C(4)), and secretion of cytokines (TNF-alpha and IL-6) in a dose-dependent manner in IgE/Ag-stimulated mast cells. Biochemical analysis of the Fc epsilon RI-mediated signaling pathways demonstrated that emodin inhibited the phosphorylation of Syk and multiple downstream signaling processes including mobilization of intracellular Ca(2+) and activation of the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and NF-kappa B pathways. When administered orally, emodin attenuated the mast cell-dependent passive anaphylactic reaction in IgE-sensitized mice. Thus, emodin inhibits mast cell activation and thereby the anaphylactic reaction through suppression of the receptor-proximal Syk-dependent signaling pathways. Therefore, emodin might provide a basis for development of a novel anti-allergic drug. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/24187http://dx.doi.org/10.1016/j.bcp.2011.08.022
ISSN
0006-2952
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약학대학 > 약학부 > Articles
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